Inhibition of inflammatory cytokine production and protection against endotoxin toxicity by benzydamine

Cytokine. 1996 Sep;8(9):710-6. doi: 10.1006/cyto.1996.0094.

Abstract

The present study was designed to assess the effect of N,N-dimethyl-3-[(1-benzyl-1H-indazol-3-yl)ossi]-1-propana mine (benzydamine) on in vivo and in vitro production of inflammatory cytokines. Benzydamine inhibited tumour necrosis factor-alpha (TNF-alpha) production in vitro by human lipopolysaccharide-stimulated monocytes with an ED50 of approximately 25 microM (12 donors). Under the same conditions, benzydamine had modest or no effect on production of interleukin (IL-1), IL-6 and IL-8. Inhibition of TNF-alpha production was not restricted to LPS in that similar results were obtained using inactivated streptococci. Inhibition of TNF production was associated with a modest (about 30% at 50 microM, 7 donors) reduction of mRNA. A similar inhibition of TNF-alpha production was also detected with mouse peritoneal macrophages. With mouse cells benzydamine also substantially inhibited IL-1 production in vitro. In vivo treatment with benzydamine (40 mg/kg s.c.) protected mice against LPS lethality. Protection against septic shock was observed when benzydamine was administered before or concomitantly with LPS. Protection against LPS toxicity was associated with a marked reduction of serum levels of TNF-alpha and IL-1 beta, whereas IL-6 was unaffected. Inhibition of inflammatory cytokine production may play a role in the anti-inflammatory activity of benzydamine and provide suggestions for novel therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Benzydamine / pharmacology*
  • Blotting, Northern
  • Cells, Cultured
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis*
  • Female
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / toxicity
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred C3H
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Benzydamine